The application of vascular immune organoids from human pluripotent stem cells in cancer immunotherapy and SARS-CoV-2 modeling

Abstract

Organoid technology has advanced our understanding of development and disease models. Organoids derived from either human pluripotent stem cells or tissue stem cells offer us the amenable platform to genetically intervene in human organ development. The advance of genetic engineering and stem cell technology pushed the limit of what organoids can do. However, the current lack of both vasculatures and immune cells hinders the understanding of how vasculatures and immune cells regulate organ development as well as their role in pathologic conditions such as cancer and infection. We have previously established a unique organoid system from human pluripotent stem cells (Ohta et al., 2019; Sugimura et al., 2020, 2017). Followed by mesodermal patterning and hemato-endothelial specification with define factors, we achieved vascular immune organoids (VIOs). We identified the highly vascularized structure of VIOs. The repertoire of cells encompasses innate immune cells such as macrophages, neutrophils, erythroblasts, and NK cells, which demonstrated functional maturity. In this talk, we will share our recent efforts in i) engineering functional immune cells for cancer immunotherapy, ii) modeling vasculitis in SARS-CoV-2 infection. We propose that VIOs could further enhance the organoid technology in both cancer immunotherapy and SARS-CoV-2 modeling. References Ohta, R., Sugimura, R., Niwa, A., Saito, M.K., 2019. Hemogenic Endothelium Differentiation from Human Pluripotent Stem Cells in A Feeder- and Xeno-free Defined Condition. J. Vis. Exp. JoVE. https://doi.org/10.3791/59823 Sugimura, R., Jha, D.K., Han, A., Soria-Valles, C., da Rocha, E.L., Lu, Y.-F., Goettel, J.A., Serrao, E., Rowe, R.G., Malleshaiah, M., Wong, I., Sousa, P., Zhu, T.N., Ditadi, A., Keller, G., Engelman, A.N., Snapper, S.B., Doulatov, S., Daley, G.Q., 2017. Haematopoietic stem and progenitor cells from human pluripotent stem cells. Nature 545, 432–438. https://doi.org/10.1038/nature22370 Sugimura, R., Ohta, R., Mori, C., Li, A., Mano, T., Sano, E., Kosugi, K., Nakahata, T., Niwa, A., Saito, M.K., Torisawa, Y.-S., 2020. Biomimetic aorta-gonad-Mesonephros-on-a-Chip to study human developmental hematopoiesis. Biomed. Microdevices 22, 34. https://doi.org/10.1007/s10544-020-00488-2